The present invention relates to catheters configured for insertion into a lumen or body cavity of a subject and is particularly suitable for insertion into the male urethra.
Conventionally, several types of thermal treatment systems have been proposed to treat certain pathologic conditions of the body by heating or thermally ablating targeted tissue. These thermal treatment systems have used various heating sources to generate the heat necessary to treat or ablate the targeted tissue. For example, laser, microwave, and radio-frequency (RF) energy sources have been proposed to produce the heat which is then directed to the targeted tissue in or around the selected body cavity. Thermal treatment systems have been used to thermally ablate prostatic tissue as well as to thermally treat or ablate the tissue of other organs, body cavities, and/or natural lumens.
One particularly successful thermal ablation system ablates the prostate by a thermocoagulation process. This thermal ablation system employs a closed loop liquid or water-induced thermotherapy (WIT) system which heats liquid, typically water, external to the body and then directs the circulating heated water into a treatment catheter. The treatment catheter is inserted through the penile meatus and held in position in the subject prior to initiation of the treatment to expose localized tissue in the prostate to ablation temperatures. The treatment catheter includes an upper end portion which, in operation, is anchored against the bladder neck and an inflatable treatment segment which is held relative to the anchored upper end portion such that it resides along the desired treatment region of the prostate. In operation, the treatment segment expands, in response to the captured circulating fluid traveling therethrough, to press against the targeted tissue in the prostate and to expose the tissue to increased temperatures associated with the circulating liquid, thereby thermally ablating the localized tissue at the treatment site. In addition, the pressurized contact can reduce the heat sink effect attributed to blood circulation in the body, thus enhancing the depth penetration of the heat transmitted by the inflatable treatment segment into the prostatic tissue.
As an acceptable alternative to surgery (transurethral resection of the prostate (TURP)), the use of WIT (water-induced thermotherapy) has been shown to be a successful and generally minimally invasive treatment of BPH (benign prostatic hyperplasia). Generally stated, the term xe2x80x9cBPHxe2x80x9d refers to a condition wherein the prostate gland enlarges and the prostatic tissue increases in density which can, unfortunately, tend to close off the urinary drainage path. This condition typically occurs in men as they age due to the physiological changes of the prostatic tissue (and bladder muscles) over time. To enlarge the opening in the prostate urethra (without requiring surgical incision and removal of tissue), the circulating hot water is directed through the treatment catheter which is inserted into the penile meatus up through the penile urethra and into the prostate as described above. The treatment segment expands with the hot water held therein to press the inflated treatment segment against the prostate, which then conductively heats and thermally ablates the prostatic tissue. The circulating water is typically heated to a temperature of about 60xc2x0-62xc2x0 C. and the targeted tissue is thermally treated for a period of about 45 minutes to locally kill the tissue proximate the urinary drainage passage in the prostate and thereby enlarge the urinary passage through the prostate.
Subsequent to the delivery of the thermal ablation (or other) treatment, the treated tissue in the prostate undergoes a healing process. Initially, the ablated tissue can expand or swell due to inflammation or edema which can undesirably block or obstruct the prostatic urethra. Further, during the healing period, portions of the treated tissue can slough off and create an undesirable and unduly limited opening size. This post-ablation or post-therapy treatment opening size can be positively influenced by xe2x80x9cmoldingxe2x80x9d the treated or ablated tissue during the healing cycle to contour the tissue about a catheter or stent held thereat. Therefore, to facilitate proper healing and to enhance the efficacy of the therapy and particularly, ablation therapy, either the treatment catheter is left in the subject for a period of time and/or a post treatment catheter, such as a conventional Foley catheter, is positioned in the subject. Conventionally, the treatment catheter can be left in the subject for about 24-72 hours after delivering the thermal treatment to the targeted tissue to reduce the likelihood that the treatment site will be injured by premature removal of the treatment catheter.
The treatment catheter typically includes insulated regions on the proximal shaft portion of the catheter to protect non-targeted tissue from undue exposure to heat as the heated fluid travels in the catheter fluid circulation passages to the desired treatment region. The insulated regions have, in the past, been provided by configuring the catheter with an extra layer or thickness of a material along the proximal or lower shaft portion. Other treatment catheters include a series of circumferentially arranged elongated air channels or conduits which encircle the heated circulating fluid passages and provide thermal insulation along the elongated shaft portion of the catheter as described in U.S. Pat. Nos. 5,257,977 and 5,549,559 to Eshel, the contents of which are hereby incorporated by reference as if recited in full herein. As the heated fluid travels through the fluid circulating passages, the insulation reduces the heat transferred to non-targeted treatment sites, such as along the penile meatus, urethral mucosa, or urethral sphincter for the BPH application. There remains a need, nonetheless, to provide improved thermal insulation for the heated circulating fluid.
In addition, the treatment catheter is typically a relatively small, thin-walled conformable or flexible catheter that is sized to be inserted into the body lumen and which usually includes a urine drainage lumen extending through the catheter. However, the catheter can deform due to exposure to the treatment temperatures over the treatment period. This deformation can, unfortunately, partially collapse the drainage lumen and, thus, reduce the urine drainage volume capacity of the treatment catheter.
It is therefore an object of the present invention to provide economical treatment catheters with improved thermal insulation regions.
It is another object of the present invention to provide catheters with enhanced thermal transfer or thermal transmissivity configurations in the treatment balloon region.
It is another object of the present invention to provide a device which can inhibit obstruction in a fluid path (such as to keep a urinary drainage path open), during and/or post-treatment with improved fluid flow volumes such that the subject is able to receive and/or discharge fluid at desired flow rates.
It is another object of the present invention to provide treatment catheters with increased drainage volume after exposure to elevated treatment temperatures.
It is an additional object of the present invention to provide methods for producing improved catheters with insulation and/or improved urinary drainage volumes.
It is yet another object of the present invention to provide methods for thermally treating a body lumen in a manner which inhibits the exposure of non-targeted tissue to excessive heat while allowing sufficient flow volume therethrough.
These and other objects are satisfied by the present invention, which provides, inter alia, flexible catheters with improved thermal insulation and/or improved drainage lumen configurations and related methods of forming same. The present invention can also provide methods of thermally treating a body lumen and methods of fabricating catheters with improved insulation or heat transfer capabilities.
More particularly, in one embodiment of the present invention, a treatment catheter can be configured for insertion into a body cavity or lumen of a subject. The treatment catheter comprises a flexible elongated tubular body having a thin outer wall with an external surface and at least one fluid lumen axially extending therein. The tubular body comprises a region having increased thermal insulation relative to another region thereof. The increased thermal insulation region extends a longitudinal length along the tubular body. The increased thermal insulation region includes a material configuration which provides sufficient thermal insulation between the at least one fluid lumen and the external surface to inhibit thermal ablation of non-targeted tissue during thermal ablation treatments.
In certain embodiments, the thermal insulation is configured to provide a temperature gradient between the temperature of the circulating fluid (which for thermal ablation procedures can be heated to about 60xc2x0-62xc2x0 C.) in the at least one fluid lumen and the external surface of the outer wall of the tubular body which is greater than about 15 degrees when measured in vitro or ex vivo. That is, the inner temperature is greater than that at the external wall outer surface. The thermal insulation can be configured to be in communication with and attached to the outer wall of the tubular body so as to provide sufficient tensile strength to allow for insertion and removal from the subject without impeding the function of the catheter.
The thermal insulation material layer can comprise a mixture of an elastomeric, rubber or polymeric material and hollow microspheres (which can be small or miniaturized hollow plastic bodies sized on the order of xcexcm). The voids provided by the hollow microspheres in the insulation layer can provide a thermal conductivity path across the integrated material layer which is interrupted to thereby provide improved thermal insulation (which impedes thermal conductivity) across the width of the material insulating layer. In certain embodiments, the polymer material is polyurethane and the in operation thermal insulation material layer can provide an increased thermal temperature gradient across the width of the material mixture layer which is greater than the same thickness of the elastomeric material alone. The improved temperature gradient can be about 10-14% greater compared to that of the temperature gradient of the same thickness of the elastomeric material alone. Further, unlike other porous materials, the microspheres, when combined with a desired polymer or elastomeric material according to embodiments of the present invention, can provide good mechanical strength between the outer wall of the catheter on one side and the outer wall of an inner lumen(s) on the other, which may not be available with other materials comprising voids (this structure can help improve the tensile strength therebetween).
The increased insulation region may be configured such that, in operation, heated circulating liquid is directed through the treatment catheter and, as it enters the tubular body, is heated to a temperature of at about at least 60xc2x0 C. and, when measured ex vivo, the external surface of the outer wall about the increased thermal insulation region exhibits a maximum temperature of about 42-45xc2x0 C. during or after a thermal treatment period of at least about 5-30 minutes.
In other embodiments, the treatment catheter can be configured with increased thermal transmissivity about the expandable treatment balloon. The increased thermal transmissivity can be provided by forming the expandable balloon wall from a suitable compound including an elastomeric substrate material such as polyurethane mixed with ceramic microspheres. The increased thermal transmissivity catheter can also include biocompatible coatings over the exterior surface of a portion of the catheter.
The present invention can provide treatment catheters configured for insertion into a body cavity or lumen of a subject which includes: (a) a flexible elongated tubular body having a thin outer wall with an external surface; (b) at least one fluid lumen axially extending within the tubular body such that the at least one lumen is encased by the outer wall; and (c) an elongated insert sized and configured to be received into the at least one fluid lumen to inhibit the closure of the fluid lumen to allow fluid throughput volumes of at least about 20 ml/min after exposure to thermal treatment temperatures during a thermal treatment session.
The thermal treatment session can expose the fluid lumen and insert to temperatures above about 45xc2x0 C. during a thermal ablation procedure. In certain embodiments, the fluid lumen is exposed to fluid in the range of about 50xc2x0-62xc2x0 C. or greater during a treatment session, which can last for at least about 5-30 minutes, and up to about 45 minutes or more, as the application demands.
In certain embodiments, the insert can be formed from a low friction material (for easy insertion into the desired fluid lumen) and/or a material which resists thermal deformation after exposure to thermal ablation temperatures and/or which is sufficiently rigid so as to retain a desired opening size for the fluid flow in the fluid lumen even when exposed in situ to compressive pressures from swollen tissue or edema. The insert can be formed from a fluoropolymer such as polytetrafluoroethylene (PTFE) having a hardness of about Shore A 98 such as Teflon, or tetrafluoroethylene (TFE), fluorinated ethylene-propylene (FEP), perfluoroalkoxy (PFA), ethylene tetrafluoroethylene (ETFE), or polyvinylidene fluoride (PVDF), and the like.
For embodiments of the catheters having a plurality of inner lumens such as an inlet channel, and outlet channel and the fluid lumen, the insert can be configured to maintain the desired fluid opening size in the fluid lumen even when the insert is exposed to increased pressures from the quantity of fluid held captured and circulating in the inlet and outlet channels about the fluid lumen.
Preferably, the insert is configured such that, after exposure to a thermal therapy including, but not limited to a thermal ablation therapy session, it allows fluid volumes of at least about 20-25 ml/min. In one embodiment, the thin outer wall is formed from polyvinylchloride (PVC) or polyurethane. The drainage lumen with the insert can be configured to allow fluid throughput volumes of above about 25 ml/min after exposure to a maximum circulating fluid temperature therein of at least about 40xc2x0-62xc2x0 C. even after exposure to these conditions for a period of about at least 40 minutes.
In one embodiment, the at least one fluid lumen is a plurality of axially extending fluid lumens and the treatment catheter further includes an inflatable treatment balloon positioned about a peripheral distal portion of the elongated tubular body. The treatment balloon is in fluid communication with at least one of the plurality of fluid lumens such that the treatment balloon is expandable to a configuration which extends outwardly a distance from the outer wall of the tubular body. The catheter may also include a thin inner tubular wall spaced apart from the thin tubular outer wall and a plurality of elongated insulation channels axially extending therebetween. The plurality of fluid lumens can include a circulating fluid inlet lumen, a circulating fluid outlet lumen, and a drainage and fluid delivery lumen. Preferably, an elongated insert is disposed in at least the drainage and fluid delivery lumen. One or more of the plurality of elongated insulation channels can be configured to encase a quantity of non-gaseous insulation material comprising polyurethane disposed therein to define an insulated region along a proximal portion of said tubular body intermediate the fluid lumens and the outer wall.
Yet another aspect of the present invention is a method of thermally treating a target region in the body. The method comprises the steps of (a) inserting a treatment catheter into a body lumen; (b) heating liquid external of the subject to above about 45xc2x0-60xc2x0 C.; (c) circulating the heated liquid in the treatment catheter such that it travels, captured in the treatment catheter, to a target treatment region; (d) exposing the tissue in the targeted region to a temperature of above about 45xc2x0 C. for a predetermined thermal ablation treatment period corresponding to the heated liquid in the circulating step; (e) insulating non-targeted tissue below the targeted region such that the non-targeted tissue is exposed to a maximum temperature of about 42-45xc2x0 C. from contact with the treatment catheter during the circulating step; (f) terminating the circulation of the heated liquid after the thermal ablation treatment period; (g) leaving the treatment catheter in the subject after the terminating step for an initial healing period of from about 12-72 hours; (h) directing body fluids to drain through the treatment catheter during the circulating, exposing, and leaving steps, wherein the treatment catheter is configured in a manner which allows a drainage volume of above about 20 ml/min (and more preferably above about 25 ml/min) after the circulating and exposing steps; and (i) removing the treatment catheter after the initial healing period.
The method can be used to treat urinary or prostate conditions such as BPH. In certain embodiments, the circulating liquid can be heated to above or about 60-62xc2x0 C. external of the subject and directed into the treatment catheter at an inlet temperature of about 60-62xc2x0C. The treatment catheter can also include a flexible drainage lumen with an elongated insert disposed therein, the elongated insert is configured to inhibit the closure of the drainage lumen and to facilitate increased urine or other body fluids drainage flow rates (or flow rates of drugs, treatment rinses, or other liquids into the body) after the exposing and circulating steps.
An additional aspect of the present invention is a method of inhibiting the closure of a flexible thin walled lumen in a catheter configured for insertion into a lumen or cavity of a biological subject. The method comprises the steps of (a) configuring a flexible elongated catheter such that it is sized for insertion into a natural body lumen or cavity of a biological subject and such that it can bend to follow the contour of the body lumen or cavity, the flexible catheter comprising at least one fluid channel therein; and (b) positioning an elongated insert into the at least one fluid channel such that it axially extends along a length thereof, the elongated insert is configured to maintain an open fluid channel during and after the flexible catheter delivers a thermal therapy to a desired target site in the biological subject.
Another aspect of the present invention is a method for providing increased thermal insulation in a treatment catheter having at least one fluid lumen therein. The treatment catheter has an outer wall which encases the at least one fluid lumen. The treatment catheter is configured to deliver thermal treatment to a target site in a natural lumen or body cavity of a biological subject. The thermal treatment can include one or more of cooling, heating, or thermal ablation treatments. The method comprises the steps of: (a) introducing a quantity of liquid insulation mixture into a desired region of the treatment catheter such that it is held intermediate the at least one fluid lumen and the outer surface of the treatment catheter; and (b) altering the physical state of the liquid mixture from liquid to a non-liquid state (or from a flowable to a non-flowing state) to define a thermally insulated region in the catheter.
In one embodiment, the treatment catheter has an elongated tubular body, and the treatment catheter further comprises a plurality of axially extending insulation lumens circumferentially arranged to encase the at least one fluid lumen below the outer wall. In this embodiment, the increased thermal insulation is carried out in the introducing step by inserting (which can include flowably injecting) the liquid insulation mixture into one or more of the plurality of insulation lumens.
In certain embodiments, the liquid insulation mixture can comprise liquid polyurethane or a liquid insulation mixture comprising initially liquid polyurethane and hollow plastic microspheres.
In some embodiments, the treatment catheters can be provided as a set of prostatic treatment catheters, each configured for insertion into the male urethra (such as for treating BPH). However, the set is provided such that each treatment balloon which expands to deliver the thermal treatment is sized a different length to allow customized fit to a particular subject (the treatment balloon which is adapted to reside in a portion of the prostatic urethra which can vary patient to patient and the catheter treatment balloon itself can be provided in lengths ranging from about 2-6 cm, typically in increments of about xc2xd cm).
Advantageously, the present invention provides flexible treatment catheters. The present invention allows, for applications which employ body fluid drainage lumens (or drug delivery or other fluids), increased rigidity about the drainage or delivery lumen which can be used to provide improved throughput volumes (increased drainage volumes therethrough) in the subject even after the catheter is exposed to elevated temperatures during thermal ablation or thermal therapy treatments.
In summary, certain embodiments of the present invention the treatment catheters can include increased thermally insulated regions compared to conventional catheters. The increased thermally insulated regions are preferably formed with selected insulative materials inserted or positioned intermediate the external wall of the catheter and the internal fluid passageways or lumens about a length of the catheter shaft which resides in the subject during treatment to inhibit non-targeted tissue from being exposed to thermal treatment temperatures. Thus, the treatment catheters of the instant invention can protect the non-targeted tissue from undesirable exposure to thermal temperatures directed to the targeted tissue during delivery of the thermal treatment. Related methods for forming the insulation in the treatment catheters such as by injecting a flowable microsphere solution into desired regions of the catheter and then solidifying to define improved insulation regions are also described.
Certain embodiments of the present invention additionally, or alternatively, provide treatment catheters which are configured to allow improved drainage and/or flow rates for other fluids such as flushing liquids to be directed into the subject therethrough. Certain of the embodiments described are particularly suitable for a subject undergoing thermal therapy or thermal ablation treatment to a localized target region in a natural body cavity or lumen such as within the prostatic urethra. The treatment catheter can remain in position for an initial portion of the healing process (temporally proximate to the post thermal ablation treatment) and can be used to deliver medicaments or rinses to the treatment region during the healing process (which in prostate treatments can promote healing and/or inhibit UTI). The treatment catheter can include one or a combination of suitable coatings such as hydrophilic coatings which can help the ease of insertion into the body cavity, antimicrobial coatings, anti-inflammatory coatings, anti-scarring coatings, and antibiotic coatings. In addition, the catheter can be used to deliver suitable fluids to the treated region to help facilitate healing and/or reduce the likelihood of infection.